Dr. Katja Hoedjes

Very broadly speaking, I am fascinated by genetic variation and how this variation controls adaptive phenotypic variation. A bit more specifically, I am interested in traits or processes are shared universally across distant animal phyla, including humans. I want to understand why adaptive variation in these highly conserved processes evolves, which genetic mechanisms control this variation, and how the evolution of a single trait correlates with or constraints other traits. I study these questions in the framework of (1) the evolution of aging and life history traits and (2) natural variation in learning and memory formation. I use a multidisciplinary approach that combines principles and techniques from evolutionary biology, ecology, genetics, neurobiology and molecular biology. I use insect species as a model, including the powerful genetic model Drosophila melanogaster, and parasitic wasps, mostly species of the genus Nasonia.

Project supported by the Novartis Foundation for Medical-Biological Research (grant 15B122) and H2020-MSCA-IF-2015 (grant 701949 "EvolAge")

Aging is universal, but there is variation in lifespan between and within species. Both diet and reproduction are well known to have a major impact on aging and lifespan, but how these two factors interact to shape the evolution of longevity remains unknown. To address this question, I have studied the genomes of experimentally evolved fruit fly populations that have adapted their life history, most notably lifespan, in response to selection for postponed reproduction and/or coping with over- or undernutrition during the larval stage. Our genome analyses revealed strong, independent responses to the two selective regimes, as well as loci that diverged in response to both regimes, thus indicating genomic interactions. Overall, our analyses suggest that naturally occurring alleles involved in longevity evolution are distinct from "aging" genes identified through classical mutant screens.

The recent advent of "-omics" tools have provided opportunities to identify genetic loci that underlie evolutionary adaptation with unprecedented genomic resolution, but only few studies have also taken the step to confirm these candidates through functional validation. I currently investigate two candidate genes, and SNPs therein, that I identified in our genome analysis: the LAMMER protein kinase Doa and the nuclear hormone receptor Eip75B. By using transgenic RNAi, association experiments and CRISPR-Cas, I aim to confirm if these candidate genes, and their SNP alleles, play a role in lifespan and other life history traits. This combination of experimental approaches will enhance our understanding of the evolution of aging, in the context of life history, and it will demonstrate how naturally occurring alleles control lifespan.

All animal species can learn and the mechanisms underlying memory formation are highly conserved, but memory dynamics vary between and within species. The opportunity to acquire new skills or to adapt behaviour through learning is an obvious benefit, but (long-term) memory formation is also costly: it can be maladaptive when unreliable associations are formed and the process of memory formation itself is energetically costly. Moreover, experimental evolution studies have shown that the evolution of enhanced memory ability may come at a cost to other fitness related traits, including lifespan, which may provide a constraint to the evolution of either trait. The genetic basis of variation in learning and memory traits, and their correlation with other traits, is unknown, however.

During my PhD project, I studied variation in long-term memory formation between closely related parasitic wasp species of the genus Nasonia. This variation is thought to reflect species-specific differences in ecology, making them ideal model species to study natural variation in memory formation. Indeed, various studies on learning in parasitic wasps had already provided valuable insights on how ecological factors affect (long-term) memory formation. The goal of my work was to investigate the genetic basis of this adaptive variation in long-term memory formation and hence merge insights from ecology, neurobiology and genetics. I took advantage of the unique genetic toolbox of the Nasonia model species; first, I backcrossed genes from N. giraulti into the genetic background of N. vitripennis, which allowed me to identify two QTL that affect long-term memory formation. Secondly, I analyzed learning-induced gene expression patterns in the heads of the two species by using Illumina HiSeq technology. These analyses have provided valuable insights into the genetic basis of variation in memory formation that can form the foundation for future research to further pinpoint the genetic loci involved in these processes.

In addition, I am interested in extending this line of research to study intraspecific variation in memory formation in Drosophila, to be able to make use of the extensive genetic toolbox for this species. Although Drosophila has long been an important model for studies on learning and memory, there is very little information on the level of variation within this species. Questions to study include: how much variation in memory formation is there within and between Drosophila populations? Is there evidence of correlation evolution of cognitive traits with life history? And, are there signatures of genomic differentiation in "memory" genes, which may be responsible for variation in learning and memory?